Search Results (280)

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

Psoriasis, a chronic immune-mediated inflammatory skin disorder, presents complex pathogenetic mechanisms potentially influenced by viral infections. This comprehensive study explored the possible interplay of resistance and viral infections among psoriasis patients using serological screening techniques. The investigation involved 90 patients aged 23–45 years, systematically examining viral seropositivity for HSV (herpes simplex virus), HZ (herpes zoster), HBV (hepatitis B virus), HIV (human immunodeficiency virus), and HCV (hepatitis C virus) through ELISA testing. The findings revealed notable active or recent viral infection rates: 8.9% HSV positivity, 2.2% HZ antibody detection, 4.4% HCV positivity, and 4.4% HIV positivity. The research can contribute to current knowledge gaps, broaden the knowledge regarding the relationship between psoriasis and viral infection, and assess resistance, as it can mediate the interaction. The results can lead to improved diagnosis, treatment, and patient care options. This study emphasizes the importance of thorough viral testing for psoriasis patients, as well as focused therapeutic regimens that take into account viral co-infections. It elucidates the complex networks of biological relationships between immune factors, contributes information that is critical to our understanding of the multifactorial etiology of psoriasis, and concludes with a strong argument for investigating the mechanisms of viral involvement in this chronic-relapsing inflammatory disease. Full article

Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)—an accurate marker of neutrophil extracellular traps (NETs)—were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients. Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, immune-mediated inflammatory disorder of the gastrointestinal tract. Immunosuppressive therapy administration increases the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation. This study aimed to investigate the hepatitis screening rate, serological status, and protective antibody levels among the Taiwanese IBD population. This single-center retrospective study included patients with IBD from January 2016 to December 2024. Hepatitis serological markers were analyzed. Patients were categorized into active HBV infection (HBsAg-positive), resolved HBV infection (HBsAg-negative and anti-HBc-positive), and non-HBV-infected groups, with prevalences of 7.5%, 32.5%, and 0.9%, respectively. This study included 347 patients with IBD (UC: 68.3%; CD: 31.7%), with a mean age of 47.1 ± 16.4 years. Patients born after 1984 demonstrated a significantly reduced HBsAg positivity (0.9% vs. 11.0%; p < 0.05) and resolved HBV infection (52.2% vs. 1.0%; p < 0.05). However, among non-HBV-infected individuals, only 42.0% had protective anti-HBs levels (≥10 mIU/mL), despite vaccination program initiation. In this study, we found an overall HBsAg positivity rate of 7.5% and an anti-HCV seropositivity rate of 0.9% in our IBD population. Taiwan’s HBV vaccination program has effectively reduced the HBV prevalence. However, a significant proportion of vaccinated individuals lack sufficient protective antibody levels, thereby requiring continued HBV screening and booster vaccinations. Full article

Purpose: This article aims to harmonize the current data from the literature, describe baseline severity, and discuss potential treatment considerations for cases of triple infection. Patients and Methods: We undertook a retrospective, observational study on 1244 patients with viral hepatitis study subgroups: chronic replicative hepatitis with HCV—679 patients, HBV—98 patients, HBV/HCV—25 patients, HBV/HDV—14 patients, and 2 patients with triple-infection (HBV, HCV, and HDV), hospitalized in the Second Department of “Sf. Cuv. Parascheva” Infectious Diseases Clinical Hospital of Galați, Romania, between 1 April 2017 and 1 March 2025. Results: Comparative analysis of biochemical parameters and liver fibrosis—at the initial testing—i.e., at the beginning of the specific antiviral therapy—with direct-acting antivirals on HCV (DAAs) or nucleos(t)ide analogues (NUCs): Entecavir (ETV) or Tenofovir Disoproxyl fumarate (TDF), for HBV, Bulevirtide (BLV) for HDV—revealed clinical forms with higher severity in the case of triple and double infections, in comparison to individuals who have had only one hepatotropic virus infection. Conclusions: Compared to patients with a single hepatotropic viral infection, those with a double or triple infection had more severe hepatic damage. Concomitant therapy with Bulevirtide, DAAs, and NUCs is possible and the therapeutic results from clinical studies, with single-infection patients showing great potential for improving the prognosis of these patients. Full article

The interplay between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and viral hepatitis, primarily hepatitis B virus (HBV) and hepatitis C virus (HCV), presents a complex challenge in managing chronic liver diseases. Recent epidemiological insights suggest an escalating prevalence of MASLD globally, attributed mainly to the obesity epidemic and associated metabolic disorders. Concurrently, chronic viral hepatitis remains a significant contributor to liver disease morbidity and mortality worldwide, despite advances in antiviral therapies. According to the World Health Organization (WHO) 2023 data, approximately 296 million people are living with chronic HBV infection (about 3.8% of the global population), and 58 million people with HCV infection (about 0.7%), together accounting for over 1.1 million deaths annually. The coexistence of MASLD and viral hepatitis presents a complex scenario in clinical outcomes, where the effects on liver health can vary. Although many studies highlight the potential for additive or synergistic worsening of liver conditions, leading to complications such as cirrhosis, liver failure, and HCC, the impact of HBV on MASLD is not consistent. Managing patients with dual MASLD and viral hepatitis is complex due to the interplay of metabolic and viral factors. Lifestyle modifications, including weight loss, dietary changes, and physical activity, are fundamental to MASLD management and help reduce fibrosis risk in viral hepatitis. This review examines the dual impact of MASLD and viral hepatitis on liver pathology and delineates shared pathophysiological mechanisms, including the influence on hepatic steatosis, inflammation, and fibrogenesis. It also discusses therapeutic strategies tailored to manage this comorbidity, emphasizing the need for an integrated care approach that addresses both metabolic dysfunctions and viral infection to optimize patient outcomes. Full article

The impact of hepatitis B virus (HBV) diversity and evolution on disease progression is not well-understood. This study aims to compare intra-individual viral evolution in two groups of chronic hepatitis B (CHB) patients, using antiviral treatment initiation as a measure of lack of immunological control. From the Danish Database for Hepatitis B and C (DANHEP), 25 CHB patients were included; 14 with antiviral treatment initiation (TI group), and 11 without (NTI group). For each patient, three serial plasma samples taken before potential treatment initiation were selected. HBV DNA was amplified by PCR and analyzed by next-generation sequencing. HBV DNA and alanine transaminase were elevated in the TI group throughout the study period. Significantly higher substitution rates in the NTI group versus the TI group were found both within the viral population and at consensus level. Putative predicted CD8⁺ T cell epitopes contained significantly more substitutions in the NTI group. Genome-wide association analysis revealed several amino acid residues in the HBV genome associated with treatment initiation. This study shows that HBV has a higher rate of substitutions in CHB patients not requiring treatment. This could be linked to host immune pressure leading to disease control. Full article

Chronic viral hepatitis B and C remain major global health challenges, contributing significantly to liver-related morbidity and mortality. Despite antiviral therapies and vaccines for HBV, progression to cirrhosis and hepatocellular carcinoma remains common. For HCV, the lack of a vaccine and high chronicity rates further complicate outcomes. Recent evidence highlights gut–liver axis dysfunction and microbiota dysbiosis in disease progression, immune dysregulation, and fibrosis. Notably, alterations in microbiota composition, including reduced commensal bacteria such as Bifidobacteria and Lactobacilli and an increase in putatively harmful Enterobacteriaceae and Veillonellaceae, have been observed in HBV/HCV infections and cirrhosis. While antiviral therapies do not directly target the gut microbiota, they can contribute to partial restoration of microbial balance by reducing hepatic inflammation and improving gut–liver axis integrity. Nonetheless, post-treatment patients remain at elevated risk of HCC due to persistent epigenetic and immune-mediated changes. Emerging interventions, including probiotic strains, prebiotics, and symbiotics, demonstrate potential in enhancing gut health, alleviating inflammation, and enhancing the quality of life for liver disease patients. Moreover, the gut microbiota is gaining increasing recognition as a potential non-invasive biomarker for early disease detection and monitoring. Ultimately, modulating the gut microbiota could become an integral component of future strategies for managing chronic liver diseases and preventing their complications. Full article

Background/Objectives: Alcohol-related liver disease (ARLD) is a major cause of chronic liver disease, yet its clinical profile in Albania, a region with high HBV prevalence and rising alcohol consumption, remains poorly characterized. This study evaluates the clinical markers of advanced ARLD as noninvasive fibrosis indicators, acknowledging limitations in observational data and the need for validation in diverse populations. Methods: In this cross-sectional study, 200 patients with ARLD were classified as having mild or advanced disease based on clinical, biochemical, and imaging criteria. Associations between socioeconomic factors, nutritional status, and fibrosis markers with advanced ARLD were assessed using multivariate logistic regression, adjusted for age, sex, smoking status, and duration of alcohol use. Results: Lower Prognostic Nutritional Index (PNI) score was significantly associated with advanced ARLD (OR 0.95, 95% CI 0.91–0.99; p = 0.014), suggesting a potential role of nutritional status in disease progression. Higher APRI and FIB-4 scores were associated with an increased risk of advanced ARLD (APRI: OR 1.27, 95% CI 0.71–2.26; FIB-4: OR 1.10, 95% CI 0.81–1.51), though these associations did not reach statistical significance. Conclusions: This study provides a first clinical assessment of ARLD in Albania, highlighting the potential role of nutritional and fibrosis markers in risk stratification. While the study design limits definitive conclusions, our findings underscore the need for larger prospective studies to validate these associations and further investigate the influence of metabolic and socioeconomic factors on ARLD progression in Albania. Full article

This study aimed to assess the prevalence of HDV (hepatitis delta virus), HCV (hepatitis C virus), and HIV (human immunodeficiency virus) coinfections among HBsAg-positive patients and to determine the severity of liver fibrosis and biochemical markers. Furthermore, the study sought to evaluate the noninvasive fibrosis scores (APRI and FIB4) in predicting the severity of liver disease in patients with hepatitis B. A retrospective analysis of 1434 patients with chronic HBV admitted between January 2020 and December 2024 was conducted at Sincan Tertiary Hospital. The positivity rates of the following antibodies were the focus of the study: anti-HDV, anti-HCV, and anti-HIV. In addition to these, the levels of HIV-RNA, HCV-RNA and HBV-DNA, as well as several biochemical markers (ALT, AST, INR, albumin, bilirubin and platelet count) were also evaluated. The APRI and FIB-4 scores were calculated. Of the 1434 patients, 49 (3.4%) tested positive for anti-HDV, 784 were screened for anti-HCV, and 749 were screened for anti-HIV. The positivity rates were 3.4% (27/784) and 3.4% (26/749), respectively. According to ROC analysis, the FIB-4 score had a statistically significant effect on predicting anti-HDV negativity (AUC = 0.59, p = 0.031). However, the APRI score was not a significant predictor for anti-HDV positivity (AUC = 0.53, p > 0.05). APRI and FIB-4 scores did not have a statistically significant discriminatory power in predicting anti-HCV and anti-HIV positivity (p > 0.05). The cut-off value for the FIB-4 score in predicting anti-HDV positivity was 1.72, with a sensitivity of 61.4% and a specificity of 42.9% (p = 0.031). Among the HCV/RNA-positive patients (n = 5), all were male, and two also had positive anti-HBe results with undetectable HBV/DNA levels. One HIV/RNA-positive patient, a foreign national, was confirmed to have HIV/HBV/HDV infection. All HBsAg-positive patients should undergo routine anti-HDV testing. Vaccination programmes are vital in preventing the spread of HDV. Dual screening strategies are essential for identifying infected individuals and developing prevention and treatment programmes. Anti-HDV positivity indicates advanced liver fibrosis, emphasising the importance of screening and monitoring. However, the limited accuracy of the APRI and FIB-4 scores for detecting coinfections highlights the need to integrate noninvasive methods with molecular diagnostics for precise management. Full article

Background/Objectives: Hepatitis B virus (HBV) infection is a worldwide health problem responsible for chronic liver disease and hepatocellular carcinoma. Both innate immunity and the adaptive immune response play central roles in the development of chronic hepatitis and liver cancer. We previously performed a comprehensive analysis of gene expression in the livers of HBV-infected chimeric mice and found that several genes associated with cell growth or carcinogenesis via hypoxia and KRAS signaling were upregulated by HBV infection. However, due to the absence of adaptive immunity in uPA/SCID chimeric mice, we were unable to analyze the effect of the host immune response. Methods: In this study, we compared gene expression profiles in the livers obtained from HBV-infected chimeric mice with those of HBV carriers. Results: After HBV infection, the expression of genes associated with inflammation and immune response, especially involving the Th1 and Th2 activation pathways, was altered as HBV-specific intracellular immune responses both in vivo and in clinical samples. Interestingly, the proinflammatory gene IL12A was induced by HBV infection in the chimeric mouse livers but not in the human livers, and associated genes, such as SRDA5A2, AR, and CCR3, showed differential alteration by HBV infection between the chimeric mouse and human livers. Conclusions: These results suggest that hepatocarcinogenesis may be suppressed by host immunity in HBV carriers. This study highlights potential new implications for inhibiting the progression of HBV-related liver diseases, including hepatocarcinogenesis. Full article

The Hepatitis B Virus (HBV) presents a formidable global health challenge, impacting hundreds of millions worldwide and imposing a considerable burden on healthcare systems. The elusive nature of the virus, with its ability to establish chronic infection and evade immune detection, and the absence of curative agents have prompted efforts to develop novel therapeutic approaches beyond current antiviral treatments. This review addresses the challenging concept of a functional cure for HBV, a state characterized by the suppression of HBV and HBsAg, mitigating disease progression and transmission without a complete cure. We provide an overview of HBV epidemiology and its clinical impact, followed by an exploration of the current treatment landscape and its limitations. The immunological basis of a functional cure is then discussed, exploring the intricate interplay between the virus and the host immune response. Emerging therapeutic approaches, such as RNA interference-based interventions, entry inhibitors, nucleic acid polymers, and therapeutic vaccines, are discussed with regard to their success in achieving a functional cure. Lastly, the review underscores the urgent need for innovative strategies to achieve a functional cure for HBV. Full article

Hepatitis B virus (HBV) infection is a leading cause of chronic liver disease and liver cancer worldwide. Hepatocellular carcinoma (HCC) remains one of the major causes of cancer-related mortality globally. Effective prevention and management strategies for HBV infection are crucial in reducing liver-related complications, including HCC. HBV plays a distinct role in liver carcinogenesis, and there is growing knowledge about the factors contributing to its oncogenic potential. With advancements in HCC management, special attention must be given to the treatment of HBV infection in patients with HBV-induced HCC. In this review, we summarize current insights into the carcinogenic mechanisms of HBV and discuss the latest approaches to managing HBV-induced HCC. Full article

Chronic hepatitis B is linked with considerable liver-related morbidity and mortality globally. Human leukocyte antigen (HLA) polymorphisms affect the susceptibility and outcome of many immune-mediated diseases and infections. Our aim was to study the impact of HLA alleles on HVB-infected individuals in a Greek population. In total, 107 patients with chronic HBV infection (cHBV group) and 101 with spontaneous clearance (SC-group) of hepatitis B surface antigen (HBsAg) were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci by single-specific primer polymerase chain reaction (PCR-SSP). The HLA alleles’ frequencies were compared between the two patient groups and healthy individuals from the North Greece Bone Marrow Donor Registry (14506 samples). We found a significantly increased frequency of HLA-C*01 and HLA-DRB1*16 alleles in the cHBV group versus the SC-group. The frequency of HLA-A*01, HLA-B*08, HLA-C*01, HLA-C*08, HLA-DRB1*03, and HLA-DQB1*05 alleles was significantly higher in cHBV patients versus healthy individuals, while the frequency of the HLA-B*38 allele was significantly lower. Our study showed an association of specific HLA alleles with either susceptibility or protection against chronic HBV infection. Full article

Hepatitis B virus (HBV) is a causative reagent that frequently causes progressive liver diseases, leading to the development of acute hepatitis, chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Despite several antiviral drugs, including interferon-α and nucleotide derivatives, being approved for clinical treatment of HBV, critical issues remain unresolved, e.g., their low-to-moderate efficacy and adverse side effects, as well as resistant strains. In this study, twenty-three matrine derivatives were synthesized, and their antiviral effects against HBV were evaluated. Of these, eleven compounds inhibited HBeAg secretion significantly more than the positive control, lamivudine (3TC). Among the compounds synthesized in this study, compounds 4a and 4d had the most potent inhibitory activity, with IC₅₀ value of 41.78 and 33.68 μM, respectively. Compounds 1h, 4a, and 4d were also subjected to molecular docking studies. These compounds inhibited viral gene expression and viral propagation in a cell culture model. Thus, we believe our compounds could serve as resource for antiviral drug development. Full article